Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives

Abstract

A series of 6- and 6,8-halocoumarin derivatives have been investigated as potential antiproliferative compounds against a panel of tumor and normal cell lines. Cytotoxic effects were determined by the MTT method. To investigate the potential molecular mechanism involved in the cytotoxic effect, apoptosis assay, cell cycle analysis, reactive oxygen species (ROS), and reduced glutathione analysis were performed. Among the screened compounds, coumarins 6,8-dibromo-2-oxo-2H-chromene-3-carbonitrile 2h and 6,8-diiodo-2-oxo-2H-chromene-3-carbonitrile 2k exhibited the most antiproliferative effect in thyroid cancer-derived cells TPC-1. The apoptosis assay showed that both 2h and 2k induced apoptosis in TPC-1 thyroid cancer cells. According to these experiments, both coumarins induced a slight increase in TPC-1 cells in the G2/M phase and a decrease in the S phase. A significant increase in ROS levels was observed in TPC-1 treated with diiodocoumarin 2k, while the dibromocoumarin 2h induced a decrease in ROS in a dose and time-dependent manner.

Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells

“…Pellet was washed with PBS, resuspended in a buffer containing PI and then incubated for 30 min. The DNA content was then detected using flow cytometry (MoFloAstrios EQ, Beckman Coulter, Brea, CA, USA) [ 36 ]. The analysis of cell cycle phase distribution was performed with Kaluza Flow Cytometry Analysis Software (Software Version 1.2, Beckman Coulter, Brea, CA, USA) by setting 3 gates in each single parameter histogram: G0/G1, S and G2/M.…”